Doxorubicin has been encapsulated into “solid” liposomes composed of a mixture of distearoyl analogs of phosphatidylcholine and phosphatidylethanol (in a 3: 2 molar ratio). The liposomes are sterically stabilized by incorporating a conjugate of dipalmitoylphosphatidylethanolamine with poly(ethylene glycol)-2000 in an amount of 5 wt % with respect to the total lipid content. The data of differential scanning microcalorimetry method show that the lipid bilayer of the doxorubicin-containing liposomes occurs in a gel-like (“solid”) state up to a temperature of 47°C. Estimated in terms of inhibition of the growth of solid and ascitic Ehrlich’s carcinoma in mice, the antitumor effect of such liposomes is equal to that of ordinary doxorubicin, whereas sterically non-stabilized “ solid” liposomes are 1.5 times less active.

The toxicity of sterically stabilized doxorubicin-containing "solid" liposomes comprising a mixture of distearoyl analogs of phospatidylcholine and phosphatidylethanol (in a 3 : 2 molar ratio) was evaluated. Upon injection of the ordinary and liposomal doxorubicin in a total dose of 12 mg/kg, the early loss of mice with implanted ascitic Ehrlich's carcinoma was 100 and 50%, respectively, and the average lifetime of the animals treated with liposomal doxorubicin was 1.6 times longer. In comparison to the ordinary doxorubicin, injections of the liposomal preparation resulted in a lower drop of the body weight (10%) and a smaller decrease in leukocyte number (12%). The results of fluorimetric measurements showed that the accumulation of antibiotic in the cardiac muscle 15 - 180 min after injection of liposomal doxorubicin was 30 - 57% lower than that upon the injection of the ordinary preparation.

The effect of anionic phosphatidylethanol on the incorporation of doxorubicin into liquid-crystalline liposomes consisting of soybean phosphatidylcholine was studied. Over 90% of doxorubicin are encapsulated in liposomes in the case of a 3 : 2 phosphatidylcholine - phosphatidylethanol molar ratio, with a doxorubicin concentration reaching 130 mg/(mg of total phospholipids). The Stokes radius of the doxorubicin-containing liposomes was found to be about 160 Е. In terms of the ability to inhibit solid Ehrlich carcinoma in mice, the obtained liposome formulations of doxorubicin were much less effective in comparison to the usual antibiotic.

Doxorubicin has been encapsulated into liposomes composed of a mixture of distearoyl analogs of phosphatidylcholine and phosphatidylethanol (in a 3:2 molar ratio). The liposomes are sterically stabilized by incorporating a conjugate of dipalmitoylphosphatidylethanolamine with poly(ethylene glycol) 2000 (5 wt % with respect to the total lipid content). The data of differential scanning microcalorimetry method show that lipid bilayer of the doxorubicin-containing liposomes occurs in a gel-like (solid) state up to a temperature of 47 °С. Estimated in terms of inhibiting the growth of solid and ascitic Ehrlich's carcinoma in mice, the antitumor effect of such liposomes is equal to that of usual doxorubicin, whereas sterically non-stabilized liposomes are 1.5 times less active.

The toxicity of sterically stabilized doxorubicin-containing “solid” liposomes comprising a mixture of distearoyl analogs of phospatidylcholine and phosphatidylethanol (in a 3: 2 molar ratio) was evaluated. Upon infusion of the ordinary and liposomal doxorubicin in a total dose of 12 mg/kg, the early loss of mice with implanted ascitic Ehrlich’s carcinoma was 100 and 50%, respectively, and the average lifetime of the animals treated with liposomal doxorubicin was 1.6 times longer. In comparison to the ordinary doxorubicin, administration of the liposomal preparation resulted in a lower drop of the body weight (10%) and a smaller decrease in leukocyte number (12%). The results of fluorimetric measurements showed that the accumulation of antibiotic in the cardiac muscle 15–180 min after infusion of the liposomal doxorubicin was 30–57% lower than that upon infusion of the ordinary preparation.

The radioprotective properties of 12 compounds of 9a-homo-13-thiaprostanoid series were investigated under gamma irradiation using the molecular model of beta-carotene radio-oxidation in oleic acid in vitro, erythrocyte radiomimetic model in ex vivo-in vitro system as well as in vivo radiation damage in mice. Most of these compounds stimulated the radio-oxidation of beta-carotene, however in this model two prostanoids with natural alpha-chain displayed radioprotective properties. Expressed membrane stabilizing effect of two 9a-homo-13-thiaprostanoid nor-analogues was revealed in radiomimetic model experiments. Two 10, 10-dimethyl-13-thiaprostanoids raised animal radioresistance during in vivo experiments.

Antiinflammatory activity and mechanism of action are studied for seven compounds of the 8,16-diazasteroid series, It is established that the antiinflammatory activity of the compounds is increased on the whole due to the reduced ketofunction in the 12 position of 8,16-diazasteroid as well as for the introduction of methoxy groups in the 2 and 3 position or phenol substitute in the 16 position. The activity of compounds VI and VII also depends on the inflammation model or on the pain reaction and differs significantly from the effectiveness of diclofenac sodium and prednisolone. Unlike the latter, the compounds under study are virtually devoid of hormonal activity.

The pharmacokinetic investigation and the study of metabolism of an immunostimulator of 8-azasteroid series were performed on a single-compartment model. The main pharmacokinetic parameters of the immunomodulator in mice were established using different routes of administration. The maximal accumulation of tritium-labeled 8-azasteroid was recorded in the kidneys, liver and lung. The character of distribution changes with time. The half-life period is in the range of from 0.69 to 1.4 hours at different routes of administration. The total clearance is 0.49 ml/min, the area under the pharmacokinetic curve--3.8-8.1 micrograms/h/ml. On the model of the monooxygenase cytochrome P-450-containing system of the liver microsomes there was confirmed the formation of two metabolites preliminarily isolated from the mouse urine. By the character of resorption, distribution, elimination this 8-azasteroid immunoactivator is close to the agents of glucocorticoid series.